This is a proposal to seek continuation of the support for the University of Pennsylvania Genetics Center. This Center was initiated in 1974 by Dr. William Mellman and has been instrumental in the development of Human Genetics at the University of Pennsylvania. The Clinical Genetics, Cell Biology, Cytogenetics and Experimental Animal Genetics have developed excellent programs which will support continuing interactive research. This proposal stresses the importance of molecular biology in the development of Human Genetics. The submitted projects represent new investigations in areas of molecular biology which integrate with the established strengths of the Center. Four Core facilities are proposed which will serve for the Administration of the Center and provide Cell Biology support, Experimental Animal Genetics expertise, and new techniques for Cytogenetic Analysis of Molecular Organization. There are six program projects which represent new directions for development. It has been recognized that the revolution in molecular biology requires revolutionary changes in the study of Human Genetics. These projects are designed to study: The Biologic Organization of Proteins, The Molecular Organization of the Histocompatibility Locus, The Developmental Consequences of Defective Collagen, The Developmental Consequences of Metabolic Disease, The Transcriptional Analysis of Double Minute Chromosomes in Transformed Cells, and A Study of Chromosomal Organization and Its Rearrangement in Translocated Chromosomes. These projects depend on the opportunities afforded by the Core facilities and lend support to each other.